Dose guides for injection syringe

ABSTRACT

The present embodiments provide for simple devices that guide the loading and dispensing of accurate small doses of fluid from standard injection syringes.

RELATED APPLICATIONS

The present application claimed priority benefit of U.S. Patent Appls.Ser. No. 61/478,748, filed Apr. 25, 2011, and Ser. No. 61/597,248, filedFeb. 10, 2012, each of which is incorporated fully herein by reference.

BACKGROUND

A hypodermic syringe is an important piece of medical equipment for manyindividuals ranging from surgeons to patients. With advancements inmodern medicine, shorter needles, longer reservoirs, and virtuallypainless injections, syringes have changed for the better. Nevertheless,it remains difficult for even skilled practitioners to load a syringewith precise volumes and administer the unit volume (e.g., dose)accurately. This is particularly important for injections wherevariations can result in adverse clinical effects, such as highly potentmedicines (e.g., insulin), in certain settings where small doses areadministered (e.g., intraocular injections), or where the care giver isless skilled or has difficulty handling the syringe loading process.There is a need in the art for simple yet accurate means for loading anddelivering more accurate volumes using standard syringes.

SUMMARY

The present invention provides for a system comprising at least onedevice that allows for accurate loading and/or delivery of precisevolumes of fluid (e.g., sample or medicament) using a standard injectionsyringe.

In some aspects of the invention, the system comprises a removabledose-loading “spacer” guide of predetermined dimensions that, in use, isplaced abutting the end of a standard syringe where the plunger extendsfrom the syringe barrel (typically placed slidably adjacent to theplunger) that is loaded with an excess of fluid (e.g., medicine), fromwhich the excess fluid is then expelled as regulated by the spacer guideto provide for an accurate loading of fluid volume (e.g., unit dose)within the syringe. The dose-loading spacer is then removed from thesyringe/plunger junction, and the remaining volume (dose) can bedelivered from the syringe.

In other aspects, the system comprises a dose-delivery guide ofpredetermined dimensions, used to deliver an accurate dose to thesubject. In use, the dose-delivery guide is placed abutting the top ofthe barrel of a syringe (i.e., where the plunger extends from thebarrel) either before or after the syringe has been loaded with fluid,then the fluid (e.g., dose of medicine) is delivered to the subject bydepression of the plunger, wherein the dose-delivery guide regulates thedelivery of the dose volume by stopping the motion of the plungeraccording to the predetermined parameters of the dose-delivery guide. Ina particular aspect, the dose-delivery guide is integral to the proximalend of the plunger rod.

In another aspect, the dose-loading spacer and the dose-delivery guideare used synergistically to provide for an accurate delivery of thedose. The dose-loading spacer defines the volume of the fluid prior toadministration and the dose-delivery guide assures a more accuratedelivery of the dose. The dose-delivery guide may be positioned beforeor after the syringe has been filled with fluid (e.g., medicine); orbefore or after the dose-loading spacer has been used. If thedose-delivery guide is in place at the top of the syringes barrel, thedose-loading spacer is positioned either over the dose-delivery guide(i.e., encompassing the guide) or adjacent to the dose-delivery guide(e.g., abutting the guide and the plunger), depending on thepredetermined parameters of the dose-loading spacer, typically but notnecessarily after the syringe has been filled with an excess of fluid.The excess fluid expelled according to the spacer to provide an accuratedose loaded in the syringe; then the dose loading spacer is removed butthe dose-delivery guide is left in place, such that the remaining fluid(dose) is delivered to the subject by depression of the plunger, whereinthe dose-delivery guide regulates the delivery of the dose volume bystopping the motion of the plunger according to the predeterminedparameters of the dose-delivery guide. In a specific embodiment, thedose-delivery guide is integral to the plunger for use with a standardglass syringe such as RD 0.5 cc Hypak™ glass syringe.

Using the system of the dose-loading spacer and, optionally, thedose-delivery guide is relatively easy, such that elderly patients orchildren of appropriate age (e.g., diabetics who inject insulin athome), can achieve precise dosing easily and accurately.

A particular aspect of the invention is a dose-loading “spacer” guidefor loading an injection syringe, the spacer having a grip portion and acollar portion, the collar portion configured to be placed at theproximal (top) end of a syringe barrel, slidably abutting an extendedsyringe plunger rod; wherein the collar is rigid and includes an openingfor receiving the extended syringe plunger, and an inner wall that bearsagainst the plunger rod for guided displacement therealong, and whereinthe collar has predetermined dimensions and, in use, stops the movementof the plunger toward the syringe barrel at a predetermined distancefrom the syringe barrel, which distance is directly related to thevolume to be loaded in the injection syringe.

Another particular aspect of the invention is a dose-delivery guide forcontrolling the volume expelled from a loaded injection syringe, thedose-delivery guide configured to be at the proximal (top) end of asyringe barrel, slidably abutting an extended syringe plunger rod;wherein the dose-delivery guide is rigid in length and includes anopening for receiving the extended syringe plunger rod, which openingallows the plunger to move freely through the guide until motion of theplunger is impeded by the guide, wherein the dose-delivery guide haspredetermined dimensions and a rigid height that, in use, stops themovement of the plunger toward the syringe barrel at a predetermineddistance from the syringe barrel, which distance is related to thevolume (dose) to be delivered by the injection syringe. Thedose-delivery guide can have a continuous circumference for placementonto a syringe plunger before the plunger is engaged with the syringe,or can have a discontinuous circumference for placement onto a plungerthat is already engaged with the syringe. The dose-delivery guide may beintegral to the plunger rod. In a specific embodiment, the dose-deliveryguide is integral to the plunger for use with a standard glass syringesuch as BD 0.5 cc Hypak™ glass syringe.

Another aspect of the invention is a dose-loading dose-delivery systemcomprising both a dose-loading “spacer” guide and a dose-delivery guidefor loading and expelling the volume (dose) of a syringe. In use, forexample, the dose-delivery guide is placed at the top (proximal end) ofthe syringe barrel, typically steadied against the plunger rod, eitherbefore or after the plunger is engaged with the syringe; excess fluid isloaded into the syringe or the syringe may have been preloaded withexcess fluid; the dose-loading spacer is placed over, or adjacent to,the dose-delivery guide, and excess fluid is expelled from the syringeas determined by the dose-loading spacer (i.e., the plunger is depresseduntil its motion is stopped by the dose-loading spacer) and thedose-loading spacer is removed; remaining fluid in the syringe is thendelivered to the subject by depressing the plunger until the plunger'smotion is stopped by the dose-delivery guide.

Alternatively, the invention is a dose-loading dose-delivery systemcomprises a removeable dose-loading “spacer” guide and a dose-deliveryguide integral to the plunger rod for loading and expelling the volume(dose) of a syringe. In use, for example, the syringe has been preloadedor is loaded with excess fluid; the dose-loading spacer is placed over,or adjacent to, the dose-delivery guide; excess fluid is expelled fromthe syringe as determined by the dose-loading spacer (i.e., the plungeris depressed until its motion is stopped by the dose-loading spacer);the dose-loading spacer is removed; remaining fluid in the syringe isthen delivered to the subject by depressing the plunger until theplunger's motion is stopped by the dose-delivery guide.

DESCRIPTION OF THE DRAWINGS

FIG. 1A is a photograph showing the top view of an embodiment of theinvention. FIG. 1B shows a side view of an embodiment of the invention.

FIGS. 2A and 2B are schematic diagrams showing dimensions of anembodiment of the invention. “N.T.S.” indicates drawings are not toscale.

FIGS. 3A to 3D illustrate use of an embodiment of the dose-loadingspacer with a conventional syringe. In FIG. 3A, the syringe has beenloaded with an excess volume of fluid; double arrow indicates themovement of the spacer into position. In FIG. 3B, the syringe guide hasbeen placed at the proximal (top) end of the syringe barrel, abuttingthe plunger rod; double arrow indicates motion of the plunger. In FIG.3C, the plunger has been depressed against the dose-loading spacer,which has regulated the expulsion of the excess fluid but caused thesyringe to retain an accurate and pre-determined amount of fluid. InFIG. 3D, the guide has been removed, and the syringe contains theaccurate dose as determined by the guide. The devices in the drawings ofFIG. 3 are not to scale.

FIG. 4A is a photograph of a syringe bearing an example dose-deliveryguide that has been placed on the syringe plunger rod (arrow), and anexample removable dose-loading spacer. FIG. 4B is a photograph of thesyringe of FIG. 4A with the dose-loading spacer placed adjacent to thedose-delivery guide, illustrating how the guides can be configured tofit together.

FIGS. 5A and 5B are photographs of example dose-loading anddose-delivery guides with predetermined measurements correlated with thevolume to be loaded and delivered. In this embodiment, the dose-deliveryguide has a greater length dimension than the dose-loading guide becausethe syringe flange at the proximal end of the barrel has an indentationthat receives the dose-delivery guide to the depth of 0.6 mm. *indicates critical measurement: tolerance should be within * 0.02 mm.ID: inner dimension; OD: outer dimension.

DETAILED DESCRIPTION

It should be understood that this invention is not limited to theparticular methodology, protocols, and reagents, etc., described hereinand as such may vary. The terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to limit thescope of the present invention, which is defined solely by the claims.

As used herein and in the claims, the singular forms include the pluralreference and vice versa unless the context clearly indicates otherwise.The term “or” is inclusive unless modified, for example, by “either.”Other than in the operating examples, or where otherwise indicated, allnumbers expressing quantities of ingredients or reaction conditions usedherein should be understood as modified in all instances by the term“about.”

All patents and other publications identified are expressly incorporatedherein by reference for the purpose of describing and disclosing, forexample, the methodologies described in such publications that might beused in connection with the present invention. These publications areprovided solely for their disclosure prior to the filing date of thepresent application. Nothing in this regard should be construed as anadmission that the inventors are not entitled to antedate suchdisclosure by virtue of prior invention or for any other reason. Allstatements as to the date or representation as to the contents of thesedocuments is based on the information available to the applicants anddoes not constitute any admission as to the correctness of the dates orcontents of these documents.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as those commonly understood to one of ordinaryskill in the art to which this invention pertains. Although any knownmethods, devices, and materials may be used in the practice or testingof the invention, the methods, devices, and materials in this regard aredescribed herein.

An embodiment of the present invention provides for a dose-loading“spacer” guide for loading the correct volume of fluid (e.g., unit dose)in a standard hypodermic syringe. The term dose-loading spacer issynonymous with dose-loading guide, but in some instances herein,“spacer” is used to further distinguish from the dose-delivery guidedescribed herein. The dose-loading spacer may be made of any suitablyrigid material, such as plastic or metal (including recycled materials)that can be sterilized or otherwise cleaned for use. It may be removableor permanent in nature. The dose-loading guide may be reusable andlong-lasting, or it may be disposable for single-use.

The dimensions of the spacer, particularly the height of the interiorwall of the collar portion, for example as shown as (104) of FIG. 1, aredesigned in relation to the volume of the syringe to be used inconjunction with the guide. This relationship can be expressed as:

v=πr ² h

where “v” is the unit volume μL (or cubic mm) to be delivered by thesyringe; “r” is the mm radius of the interior of the syringe cylinder;and “h” is the mm length that the plunger has to travel to deliver theunit volume. For example, in a Becton Dickenson 28 gauge insulin syringe(product no. 309300), r=1.475 mm (one-half of the diameter of 2.95 mm).In this syringe, every 1 mm in length corresponds to 6.83 μL volume. Ifthe unit volume to be delivered is 7.5 μL, (i.e., v=7.5); a spacerhaving a collar height of 1.1 mm (i.e. h=1.1 mm) can be used to measurea 7.5 μL dose (i.e., 7.514=(3.14)(1.475)²(1.1). Thus, one skilled in theart can use the volume dose and diameter of a given syringe to designthe corresponding collar dimension. In a particular embodiment, a guidehaving a 1.1 mm collar is used to accurately load a 7.5 μL dose.

The handle portion of the spacer may be of any practical design (e.g.,shape or texture) that allows the user to grip the guide for placementon (and, optionally, removal from) the syringe, e.g., on the top of thesyringe barrel abutting the plunger rod. The handle portion may bemanufactured contiguous to the collar, or may be connected (eitherdetachably or fixed) to the collar portion by any other approach. Thedose-loading guide may also bear a label or instruction(s).

As noted, the dose-loading guide of the present invention may be usedwith commercially available syringes. Because the spacer is useful foraccurately loading small volumes, typically the syringe used will be forsmall-dose administration, such as a tuberculin syringe (BectonDickinson, Franklin Lakes, N.J.) or an insulin syringe (BectonDickinson), for example, BD 3/10 cc Insulin Syringe, or BD 0.5 cc Hypak™glass syringe. The present dose-loading guide can also be used in otherapplications where accurate and repeatable volumes are required, forexample syringes used to load chromatography samples such as HPLC orautosampler syringes (e.g., Hamilton Syringes, Sigma Aldrich, St. Louis,Mo.).

In use, the hypodermic syringe is loaded with fluid (e.g., medicine,drug, formulation, therapeutic agent, placebo, or sample) in excess ofthe amount needed for the actual dose. Air bubbles may be tapped out ofthe syringe and needle. The dose-loading guide is then placed on theproximal (top) end of the syringe barrel, abutting the plunger rod(typically where the plunger enters the syringe barrel), and the plungerdepressed until the collar portion of the spacer stops the motion of theplunger. In this process, excess fluid is expelled from the syringe,leaving an accurate dose loaded in the barrel of the syringe asdetermined by the size of the collar portion of the dose-loading spacer.The guide may then removed, such that the plunger may be depressed fullyas the dose is delivered. For example, a dose-loading guide can be usedto accurately load 7.5 μL using a standard, commercially availabletuberculin syringe.

Referring to the Drawings, FIG. 1 shows an embodiment of the syringedose-loading guide/spacer (100). The spacer has a grip portion (101)that serves as a handle or other means whereby the user can position theguide. The guide has a collar portion (102) that defines an opening(103) that is, in use, placed by the user such that it abuts the top endof a standard syringe. In use, the movement of the plunger rod into thebarrel of the syringe is impeded by the height of the spacer (104). FIG.2 presents measurements of particular parts of a dose-loading spacerembodiment.

Referring to FIG. 3, a standard, commercially available syringe (305) isloaded with formulation for injection (306), in an amount in excess ofthe desired dose. The guide (300) may be held by the grip portion (301)such that the collar portion (302) opening (303) abuts the proximal endof the syringe barrel (308), e.g., at the distal end of the extendedsyringe plunger rod (307). As indicated by the double arrow in FIG. 3B,the plunger (307) is then depressed into the barrel of the syringe (305)until the proximal end of the plunger (309) contacts the guide (300), asshown in FIG. 3C. Thus, the dose remaining in the syringe (306) isregulated directly by the dimension of the guide (304). Then, the guidemay be removed, as shown in FIG. 3D, and the syringe is ready for thedelivery (e.g., administration) of the accurately loaded dose.

Another aspect of the invention provides for a dose-delivery guide thatcan used without or in conjunction with a dose-loading guide toaccurately deliver small volumes of fluid (e.g., medicament,pharmaceutical composition, sample, etc.) to a target (e.g., a subjector device). The dose-delivery guide has predetermined dimensions,designed to fit at the top (proximal) end of a standard syringe orintegral to the plunger rod. The guide is optimally designed to remainstably in place on the syringe during use and does not have to be heldin place by the user as the syringe is being used to deliver the dose.For example, the guide may be shaped to fit along and substantiallyaround a syringe plunger rod and allow the plunger rod to move throughthe guide, or the guide may be integral to the plunger rod. Thisconfiguration allows the user to inject the syringe with one handholding the syringe and the other hand free for any particular use. Thecircumference of the dose-delivery guide may be deformable or rigid,continuous or non-continuous, such that it may be placed abutting thesyringe plunger either before or after the plunger is engaged with itssyringe, respectively. The guide may be removable or permanent. Theguide may be configured to be placed on the syringe either before orafter the syringe is loaded. The dose-delivery guide must maintainrigidity along its height (i.e., the dimension related to the dosevolume). The dose-delivery guide may be made of any suitable material.e.g., metal or sterilizable plastic, which maintains dimension along thelength of the guide.

The use of the dual dose-loading and dose-delivery system isadvantageous where syringe devices have deformable plunger/syringeinterfaces, such as rubber ends, where the pressure exerted by the usercan lead to a larger volume being delivered than is intended. Becausethe distance the plunger travels within the syringe barrel is fixed bythe height of the dose-loading spacer and the height of thedose-delivery guide (rather than the depression of the plunger againstthe syringe), a more precise and accurate volume of medication can beadministered. The difference in the dimensions of the height of thedose-loading spacer and the height of the dose-delivery guide arecalculated from the formula:

V=πr ² h

where V is the volume delivered, r is the radius of the inner dimensionof the syringe barrel and h is the distance the piston has to travelalong the length of the syringe barrel. For example, if the dose volumeto be delivered is 7.5 μL, then:

V=7.5 μL or 7.5 mm³

r=2.3 mm (diameter was measured to be 4.6 mm)

V=πr ² h, or h=V/πr ²

h=7.5 mm³/(3.14)(2.3 mm)(2.3 mm)=0.45 mm

Thus, the difference in the dimensions of the height of the dose-loadingspacer guide and the height of the dose-delivery ring guide for asyringe with inner dimension 4.6 mm and for the loading and delivery ofa dose of 7.5 μL was calculated to be 0.45 mm.

As can be seen from FIG. 4, the dose-delivery guide can be shaped as aring or cylinder, or it can have any shape of predetermined dimension.In use, the guide is placed on the syringe, typically at the “top” orproximal end. In the specific example shown in FIG. 4, the guide can beplaced around the plunger rod of the syringe (FIG. 4A). In FIG. 4, thedose-delivery guide's inner dimension (I.D.) is slightly larger than theouter dimension (O.D.) of the plunger, such that the guide can movefreely along the length of the plunger. In other words, in FIG. 4, theplunger moves through the dose-delivery guide. In the specificembodiment shown in FIG. 4, the dose-delivery guide is a continuousmetal “ring,” and can be placed on the plunger before the plunger isengaged with the syringe, or before or after the syringe is loaded.Alternatively, the dose-delivery guide may have an opening on thecircumference to allow it to deform and “snap on” an extended plunger,substantially surrounding the plunger so that it may be released by theuser and maintain its position along the plunger. The dose-deliveryguide can be removeable or permanent.

The guide can be used without or with the dose-loading spacer describedherein. In a particular embodiment, the dose-delivery guide isconfigured to fit snuggly into the opening of the dose-loading spacerguide (FIG. 4B). Alternatively, the dose-loading spacer is configured toabut either end of the dose-delivery guide.

In use, the dose-delivery guide is placed on the syringe either beforeor after the syringe is loaded with fluid. The amount of fluid loadedmay be determined in traditional fashion (e.g., by visual inspection),without use of a dose-loading spacer. In this circumstance, thedose-delivery guide is advantageous when the syringe is somewhatdeformable, such that the dose delivery guide adds stability and thusbetter control over the dose delivered.

When used with the dose-loading spacer, the dose-delivery guide isplaced on the syringe either before or after the syringe is loaded withfluid; the syringe is loaded with excess fluid; the dose-loading guidespacer is placed over/against the dose-delivery guide; the plunger isdepressed until the dose-loading spacer stops the motion of the plunger,expelling excess fluid; the dose-loading guide is removed; the syringeneedle is placed where the fluid is to be delivered; the plunger isdepressed until the dose-delivery guide stops the motion of the plunger,delivering the fluid (e.g., administering the medication). In otherwords, the plunger travels along the length of the syringe barrel frompoint A to point B, the distance between point A and B is directlyrelated to the height of the dose-loading spacer and the height of thedose-delivery guide, and related to the volume (dose) to be delivered bythe syringe.

Referring to FIG. 5, this embodiment illustrates a system of a dualdose-loading spacer (FIG. 5A) configured for use with a dose-deliveryguide (FIG. 5B). This example was designed for use with a BD 0.5 ccHypak™ glass syringe with a BD PrecisionGlide™ 27 G ½″ needle to delivera dose of 7.5 μL. In this example, the syringe has a depression at theproximal end in which the dose-delivery guide inserts 0.6 mm. Thus, thedimensions of the dose-delivery guide has a longer height than that ofthe dose-loading guide, 8.01 mm compared to 7.86 mm spacer,respectively, to account for the depression in the syringe and stillguide the accurate delivery of a 7.5 μL dose.

The dose-loading guide, dose-delivery guide, and the dual guide system(dose-loading/dose-delivery guides) of the present invention areparticularly useful in circumstances where precise volumes of medicationor sample are required. For example, delivery of a precise volume can beimportant when a pharmaceutical is very active such that a small amountresults in significant biological activity (such as insulin); or where apharmaceutical may have side-effects if a non-precise volume isdelivered; or where the site of administration is small, such as in theeye (for example, IBI-20089, IBI-10090, LUCENTIS® ranibizumab injection,AVASTIN® bevacizumab, or VEGF Trap-Eye).

The dose-loading guide, dose-delivery guide or dual guide system of thepresent invention may also be included in a kit. The kit may include atleast one guide or dual guide system; or may include a first guide ordual guide system for loading a first dose unit, and a second guide orsecond dual guide system for loading a second dose unit volume, etc. Thekit may include at least one syringe for use with the guide or dualguide system. The kit may include a pharmaceutical or other activeagent, a standard (e.g., for use with analytical detection), ormaterials for user practice (e.g., saline). The pharmaceutical may bepreloaded into the syringe, e.g., excess pharmaceutical has beenpreloaded into the barrel of the syringe.

EXAMPLES Example 1. Improvement of Small Volume Syringe-Loading Accuracywith Dose-Loading Spacer

This example was designed to determine the standard deviation of using a28 gauge syringe to deliver 7.5 μL of a sustained release composition(IBI-10090, having a density of ˜1.15 mg/μL), with or without adose-loading “spacer” guide.

Four people were given ten commercial insulin syringes (28 gauge); foreach syringe, about 10 μL was drawn directly from a sample vial. Excesssample was expressed until approximately 7.5 μL was retained in thesyringe as determined visually (i.e., by “eyeballing” the correct unitvolume). The unit volume was then injected into a tared vial and theweight recorded. This was repeated for all ten syringes.

The same four people then withdrew about 10 μL of sample and expressedthe excess volume with the aid of the removable dose-loading guide asdescribed herein until approximately 7.5 μL was retained in the syringeas determined by the collar portion of the dose-loading guide. The unitvolume was then injected into a tared vial and the weight recorded. Thiswas repeated for all ten syringes. The data are shown in Table 1:

TABLE 1 Comparative accuracy of syringe loading, dosing, without or withguide without dose-loading guide with removable dose-loading guide User1 2 3 4 1 2 3 4 Syringe (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) 1 7.2310.85 9.47 7.76 9.52 9.50 9.55 8.15 2 7.54 10.11 7.06 9.56 9.62 9.949.01 8.18 3 7.47 9.50 9.36 10.09 8.93 9.37 8.25 9.08 4 8.47 9.96 13.366.12 9.60 8.44 7.70 8.30 5 7.10 10.11 12.43 9.85 8.70 8.55 8.48 8.89 69.23 11.20 7.94 10.47 8.48 7.63 9.07 8.15 7 9.54 8.51 10.42 8.99 9.208.10 8.06 7.89 8 8.32 8.45 10.28 10.06 9.75 8.12 8.74 8.06 9 9.19 11.9410.72 8.99 8.43 8.15 9.62 8.39 10 9.09 10.06 11.53 7.30 8.79 9.23 7.758.11 Average weight (mg) 9.39 Average weight (mg) 8.68 SD 1.57 SD 0.63RSD 16.68 RSD 7.28 Average volume (μL) 8.17 Average volume (μL) 7.48 SD1.36 SD 0.55 RSD 16.68 RSD 7.35

As can be seen from the data in Table 1, significant accuracy wasachieved by using the dose-loading spacer device.

In several additional experiments using the removable dose-loadingguide, syringes were loaded with a pharmaceutical composition using theguide, and accuracy was demonstrated as shown in Table 2:

TABLE 2 Accuracy of 300 guided 7.5 μL doses # syringes # users Total avemg ave μL 10 10 100  8.72 ± 1.05 7.58 ± 0.91 10 10 100 8.454 ± 0.79 7.43± 0.69 10 10 100  8.55 ± 0.68 7.50 ± 0.59

A further set of data was collected using water, as shown in Table 3:

TABLE 3 Accuracy of 100 guided 7.5 μL doses # syringes # users Total avemg ave μL 10 10 100 7.53 ± 0.44 7.53 ± 0.44

Example 2. Dual Dose-Loading/Dose-Delivery Guide System

In early experiments, using a 8.45 mm dose-loading spacer and a 8.00 mmdose-delivery ring with the BD 0.5 cc Hypak™ glass syringe attached witha BD PrecisionGlide™ 27 G ½″ needle, the volume delivered was higherthan the expected 7.5 μL. After careful examination of the BD Hypak™syringe, it was found that the flange of the proximal end of thesyringe, where the plunger rod enters the syringe barrel, is notperfectly flat; but rather it has a 0.6 mm depression or groove in whichthe delivery-guide actually seats into or sinks in. The dimensions ofthe dose-loading guide and the dose-delivery guide were then re-designedto make a 7.85 mm spacer and corresponding 8.0 mm ring, which resultedin the more accurate delivery of a ˜7.5 μL dose. Table 4 shows datacompiled using this dual guide system for a fluid having a density of1.16 gm/mL (1.16 mg/μL), such that 8.62 mg/1.16 mg/μL=7.43 μL.

TABLE 4 Delivery of 7.5 μL using dual dose-loading dose-delivery guidesystem Syringe # 1 2 3 4 5 6 7 Weight (mg) Volume (μL) 9.10 8.89 8.658.27 8.27 9.37 8.71 9.18 8.69 9.16 8.20 8.90 9.69 7.29 8.55 8.22 9.177.98 8.57 9.99 7.91 8.38 8.54 8.94 8.70 8.79 8.92 8.37 9.96 9.03 8.998.34 8.58 9.33 8.06 8.44 8.35 8.62 8.32 8.67 9.20 6.89 8.88 8.71 9.028.56 8.32 8.56 7.28 8.85 8.41 9.11 8.65 8.89 8.41 7.98 8.97 8.08 8.448.20 8.79 7.93 7.87 9.12 8.80 8.88 8.18 8.47 9.42 8.50 Average 8.94 8.578.90 8.34 8.63 9.08 7.89 8.62 7.43 SD 0.46 0.31 0.25 0.23 0.22 0.63 0.580.55 0.47 RD 5.12 3.56 2.81 2.75 2.59 6.91 7.38 6.39 6.39

1-22. (canceled)
 23. A dose-loading guide for loading an injectionsyringe, the dose-loading guide comprising: a grip portion; and a collarportion connected to the grip portion; wherein the collar portion isrigid along its height, the collar portion defines an opening thatremovably receives a dose-delivery guide during dose loading of aninjection syringe, and the collar portion is configured to stop movementof an extended syringe plunger rod into an injection syringe barrel at apredetermined distance defined between the proximal end of the injectionsyringe barrel and the distal end of the plunger rod; wherein thedose-delivery guide has a height, the difference between the collarportion height and the dose-delivery guide height corresponds to avolume of fluid to be delivered by the syringe, and, if the syringebarrel comprises a depression in which the dose-delivery guide will sit,the difference corrects for the depression; and wherein the grip portionfacilitates positioning of the collar portion around the dose-deliveryguide and along the plunger rod during dose loading, and the gripportion facilitates removal of the dose-loading guide after dose loadingis complete.
 24. The removable dose-loading guide of claim 23, furthercomprising an indication of a dose volume to be retained by theinjection syringe after use of the dose-loading guide.
 25. Thedose-loading guide of claim 23, wherein the collar portion is integralto the grip portion.